The basic premise of this proposal is that the development of rational approaches for treating and, ultimately, preventing peridontal infections will require fundamental information regarding the types of bacteria which are associate with various forms human periodontal disease, their pathogenic potential and natural patterns of colonization, and the factors which regulate their oral ecology. The comprehensive research program submitted aims to identify bacteria which are associated with: 1) rapidly-destructive forms of human periodontal disease and chronic periodontitis, 2) cemental carious lesions which are common secondary sequelae of periodontal infections and 3) initially-developing enamel carius lesions ("white spots"). The pathogenic potential of bacteria will be assessed in experimental animals, particularly the gnotobiotic rat. Techniques will be developed to facilitate the isolation, enumeration and identification of important organisms associated with human dental diseases. The age of acquisition and the patterns of intraoral colonization of organisms already found to be associated with periodontosis and rapid periodontitis will be determined in human populations. The influence of host age on susceptibility to infection by Streptococcus mutans, Actinomyces species and Bacteroides melaninogenicus will be evaluated in sub-human primates. Other basic studies will test the concept that specific adhesive interactions between bacteria and host tissue determine to significant extent the resistance or susceptibility of different hosts and tissues to bacterial infection. The role of pili in the virulence of B, melaninogenicus and its colonization in the gingival sulcus will be evaluated. The chemotactic properties of oral motile bacteria will be studied and related to their colonization of the gingival crevice area.